Attention Deficit/Hyperactivity Disorder (ADHD) is a common syndrome of unknown etiology which has onset before 7 to 8 years of age. ADHD is a marked source of both behavioral and educational difficulties in early life and can result in persistent social and work related difficulties throughout life. A variety of recent clinical and follow-up studies have suggested that ADHD is a heterogeneous disorder and that a major source of the morbidity of ADHD is the presence of other psychiatric disorders, both in childhood and developing later in life. ADHD and comorbid conditions appear to cluster in families, suggesting that there are important genetic factors which contribute to the etiology and course of the disorder. The long-term goal of this proposal is to identify genes which contribute to the etiology of Attention Deficit/Hyperactivity Disorder. The specific goal of this application is to determine the mode or modes of transmission of illness within families. In order to identify the most familial forms of ADHD, we will identify families for intensive study by screening an epidemiologically ascertained sample of twins from the state of Missouri. The parents of 3000 twin pairs which have been randomly selected from birth records will be interviewed by telephone to identify the presence of ADHD and related conditions in twins. Twin pairs in which at least one twin receives a definite or probable diagnosis of ADHD (DSM-III-R or DSM-IV subtypes) will be interviewed personally. The extended relatives of 160 to 180 twin pairs in which at least one twin received a consensus diagnosis of definite ADHD will then be systematically interviewed for the presence of ADHD and related disorders. These data will be used to estimate unbiased rates of ADHD and related conditions in the general population of twins and to determine transmission models for ADHD subtypes in extended families. Blood samples will also be collected during this study to serve as a resource for future DNA analyses. These studies should not only improve the estimation of risk for ADHD and related conditions in the general population sample (which will allow for better public health planning and intervention), but will also be the first epidemiologically ascertained family study of this common and frequently debilitating condition. Once identified, the extended families will be an important resource for future studies to identify genetic etiologies of ADHD.